Induced pluripotent stem cell (iPS cell) means a cell having pluripotency, which is obtained by reprogramming a somatic cell. Several groups including the group of Professor Shinya Yamanaka et al. of Kyoto University, the group of Rudolf Jaenisch et al. of Massachusetts Institute of Technology, the group of James Thomson et al. of the University of Wisconsin, and the group of Konrad Hochedlinger et al. of Harvard University have succeeded in producing such induced pluripotent stem cells. The induced pluripotent stem cells have attracted great interest as ideal pluripotent cells having neither immunological rejections nor ethical issues. For example, International Publication WO2007/069666 describes nuclear reprogramming factors for somatic cells that include the gene products of Oct family gene, Klf family gene and Myc family gene, and nuclear reprogramming factors for somatic cells that include the gene products of Oct family gene, Klf family gene, Sox family gene and Myc family gene. This publication also describes a method for producing induced pluripotent stem cells by nuclear reprogramming of somatic cells, which comprises a step of allowing the aforementioned nuclear reprogramming factors to come into contact with somatic cells.
The induced pluripotent stem cells can be produced using, as materials, somatic cells such as human skin fibroblasts or blood cells, regardless whether such somatic cells are derived from a healthy person or a patient. As with embryonic stem cells (ES cells), the induced pluripotent stem cells have a latent capacity to differentiate into all types of cells, and also, they are able to grow inexhaustibly if they are cultured under appropriate conditions. Moreover, the induced pluripotent stem cells are cells on which gene introduction can be easily carried out by applying a method such as electroporation. On the other hand, since production of the induced pluripotent stem cells does not require human embryo, it can be apart from an ethical problem which poses an impediment to the use of embryonic stem cells. Today, a new method for producing induced pluripotent stem cells has been developing, and it is anticipated that a more efficient technique of producing induced pluripotent stem cells, has low risk when used, will be developed in the future.
Alzheimer's disease is a disease whereby progressive functional damage and deciduation occur in nerve cells in the brain, and this is a causative disease of many dementia cases. In addition, the risk of developing this disease increases with aging, and thus it is predicted that, in the future, this disease will cause socially and medical-economically more serious problems in various countries in which the population ages. At present, there are no effective therapeutic methods that are able to suppress the progression of this disease, and thus, it is strongly desired to develop a method for treating Alzheimer's disease based on elucidation of the mechanism for the development of this disease. Senile plaques found in the brain tissues in the autopsy case of Alzheimer's disease comprise, as a main ingredient, a polymerized β-amyloid peptide (Aβ1-42) generated as a result of limited degradation of an amyloid precursor protein (APP). With regard to the mechanism for the development of this disease, numerous findings that have been obtained so far indicate that it is most widely believed that a β-amyloid peptide that forms an oligomer or a large number of β-amyloid peptides that are polymerized and become insolubilized are causative substances that cause the functional damage and deciduation of nerve cells. One reason for an increased risk of developing the disease together with aging is that the expression level of protease assuming a role in decomposition of β-amyloid, such as neprilysin in local sites decreases together with aging, so that the balance between generation and decomposition is disrupted. Taking into consideration such a mechanism for the development of the disease, if a β-amyloid peptide can be decomposed or eliminated by some method, it is anticipated that such a method can be applied as an effective method for treating this disease. Although intensive studies have been conducted to develop an agent for decomposing β-amyloid or suppressing the generation thereof; there have not yet been developed any agents whose effects could be confirmed as of the present time.
A therapeutic method of removing a β-amyloid peptide via an immune response has also been studying, In an experiment in which Alzheimer's disease model mice were used, a β-amyloid peptide was administered as a vaccine to the mice, and an immune response to this vaccine was then induced. As a result, it was found that accumulation of the β-amyloid peptide and neurological symptoms could be suppressed. On the basis of these results, a clinical test regarding vaccine therapy was carried out. However, since encephalitis was provoked in some cases, this test was suspended. Recently, the results of a follow-up study of a case, in which a vaccine had been administered before the suspension of a clinical test, have been reported. Even in such a vaccine administration case, significant clinical effects were not obtained by the vaccine administration. It has been reported that the onset of the disease can be suppressed by administering a monoclonal antibody directed against a β-amyloid peptide to Alzheimer's disease model mice in an experiment using the mice. On the basis of these results, there has been performed a clinical test in which a monoclonal antibody directed against a β-amyloid peptide has been administered to patients. However, significant clinical effects have not yet been obtained as of the present time.
Moreover, it has also been known that an aggregate of abnormal proteins causes neuronal death in neurodegenerative diseases other than Alzheimer's disease. Examples of such neurodegenerative diseases include prion disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Furthermore, in so-called polyglutamine disease including Huntington's chorea as a typical example, neuronal death is caused by aggregation of polyglutamine proteins. Amyloidosis is a disease whereby an abnormal protein called amyloid is deposited and it causes the dysfunction of organs. Familial amyloid neuropathy is a representative example of systemic amyloidosis in which amyloid is systemically deposited in many organs. In such familial amyloid neuropathy, abnormal transthyretin proteins are generated and accumulated due to abnormality in a transthyretintransthyretin gene, and as a result, dysfunction is developed in various types of organs, such as peripheral neuropathy and autonomic neuropathy, are developed. There are no effective therapeutic methods for many diseases caused by such abnormal protein accumulation under the present circumstances. As in the case of Alzheimer's disease, if abnormal proteins that cause the onset of the diseases can be removed or decomposed, it is anticipated that such means can become an effective therapeutic method.
Neither surgical excision nor radiotherapy is effective for solid cancer having multiple metastasis foci and malignant tumor such as leukemia. If effective chemotherapeutics cannot be found, the disease is untreatable. Recently, as a new method for treating cancer, an antibody therapy, namely, a method of administering a monoclonal antibody that specifically recognizes a molecule expressed on the surface of a cancer cell (a cancer cell surface antigen) has been developed. Specifically, a therapeutic method of administering a monoclonal antibody directed against HER2 expressed on the breast cancer cell surface is a standard treatment for breast cancer. Moreover, for B cell lymphoma that accounts for 70% to 80% of all types of malignant lymphoma, an antibody therapy for administering a monoclonal antibody directed against a CD20 antigen expressed on B cells has been established. As a mode of action of such antibody therapy, there has been known antibody-dependent cellular cytotoxicity (ADCC), in which immunocytes (macrophages or natural killer cells) that express a Fc receptor (a receptor that binds to a Fc portion which is a constant region of an antibody) at a high level attack cancer cells, on the surface of which an antibody binds. Since antibody-dependent cellular cytotoxicity depends on the functions of immunocytes that are originally present in a body, whether or not a sufficient functional level of or a sufficient number of immunocytes are present in a body becomes one factor that influences the effectiveness of the treatment. In general, it has been known that the functions of immunocytes often decrease in cancer patients. It is considered that a macrophage, which specifically recognizes a cancer cell and then performs phagocytosis on or attacks it, can be produced by introducing a gene of an antibody directed against a cancer cell surface antigen into a macrophage. However, the number of macrophages or monocytes as precursor cells thereof, which can be separated from a human body, is limited, and artificial gene introduction into these cells is not easy.
Patent Document 2 describes: a method of differentiating the embryonic stem cells of a primate into dendritic cells; a method of producing dendritic cells from the embryonic stem cells of a primate; dendritic cells obtained by the aforementioned production method; use of the dendritic cells for the production of a pharmaceutical agent for treating diseases, on which the therapeutic effects can be obtained by antigen-specifically controlling immune response; and a cell medicine used for the treatment of the above-mentioned diseases.